PJP

Question 1

Microbiology of PJP

Answer 1

• Unicellular, yeast-like fungus
• Obligate intracellular pathogen
• Present in most humans–>Non-pathogenic in immunocompetent hosts

=>Exists in 3 forms->Spores, Cysts and Trophic forms
90%of PJP–> Trophic forms

=>Unique cell wall composition
* Contains cholesterol instead of ergosterol-> hence :
->Rarity of extrapulmonary invasion&
->Ineffectiveness of standard antifungal agents eg- polyenes and Azoles which act on Ergosterol.
=>Echinocandins reduce the cystic forms becaus only cystic forms express beta glucans (target for echinocandins)

Question 2

Assessment:
* History
* Examination
* Investigations

Answer 2

=>History:
->High-risk patient groups include:
* Haematological malignancy
* Bone marrow transplant
* Solid organ transplant
* Autoimmune disease on immunosuppression
* Immunodeficiency states
* Immunosuppression (predominantly directed to T-cells eg- Purine analogues
* HIV (AIDS-defining illness)-> CD4 count <200/mm3
* Corticosteroids ≥15 mg prednisolone/day for> 6 weeks

Question 3

Symptoms

Answer 3

* Subacute onset (2–5 weeks)
* Symptoms often out of proportion to examination
* Fever
* Dry cough
* Chest pain
* Progressive dyspnoea → respiratory failure

Question 4

Examination

Answer 4

• Tachypnoea, tachycardia
• Hypoxia–>Often worse on exertion
• Fine crepitations
• Disease usually confined to lungs
• Extrapulmonary pneumocystosis extremely rare

Question 5

Investigations

Answer 5

=>Biochemistry
* Raised LDH (often >460 IU/L)-> Nonspecific, not diagnostic
* Procalcitonin-> Usually low or modestly elevated

=>Imaging (supportive, not diagnostic)

->Chest CT:
* Diffuse ground-glass opacities
* Interstitial perihilar and apical infiltrates
* Peripheral sparing
* Cystic changes
* Radiology is variable → cannot confirm diagnosis alone

Pearls
* Think PJP when symptoms are severe but exam is mild
* Subacute hypoxic respiratory failure in an immunosuppressed patient
* Raised LDH supports but does not diagnose
* CT is supportive only — diagnosis is clinical + microbiological

Question 6

Diagnosis

Answer 6

=> P. jirovecii cannot be cultured
→ Diagnosis relies on microscopy and/or molecular detection from respiratory samples

=>Microscopy (Definitive)

->Common stains:
* Wright–Giemsa
* Gram–Weigert
* Grocott’s methenamine silver (GMS)
* Modified Papanicolaou

->Classical histological finding:
* Foamy alveolar casts on lung biopsy

Question 7

Invx cont..
Microscopy

Answer 7

=>Sputum
* Low sensitivity unless induced (hypertonic saline)
* Sensitivity ≈ 50%
* Negative sputum does NOT exclude PJP

=>Bronchoalveolar lavage (BAL)
* Gold standard specimen for PCR
* Sensitivity ≈ 98%
* Specificity ≈ 91%
* Preferred test in critically ill patients

=>PCR on Respiratory smaples:
* High sensitivity, but interpretation required due to colonisation

Question 8

Invx cont..
β-D-Glucan

Answer 8

• Cell wall component of fungi
• Often elevated in PJP
• Not specific
• Also positive in Candida and Aspergillus
• Useful as adjunct, not confirmatory

• Diagnosis commits patient to prolonged toxic therapy
  
  • BAL PCR + microscopy = highest diagnostic confidence
  • Negative sputum is meaningless
  • β-D-glucan supports diagnosis but cannot confirm PJP alone
  • Always interpret results in clinical context of immunosuppression

Question 9

Antimicrobial Treatment of Pneumocystis jirovecii Pneumonia

Answer 9

=>Key pharmacological principle
* P. jirovecii does not contain ergosterol
→ Azoles, polyenes, allylamines are ineffective

=>Susceptible due to:
* Dihydropteroate synthase → inhibited by sulfamethoxazole
* Dihydrofolate reductase → inhibited by trimethoprim
* Treatment targets folate synthesis

Dihydropteroate synthatase also helps in De Novo Folate synthesis in PJP

Question 10

Tt

Answer 10

=>First-line Therapy

Trimethoprim–sulfamethoxazole (TMP–SMX)
* Drug of choice

->IV dose
* Trimethoprim 5 mg/kg/day
* Sulfamethoxazole 25 mg/kg/day
* Max dose: 480 mg TMP / 2400 mg SMX

->Duration–>21 days

Question 11

Second-line / Alternative Agents

Answer 11

• Dapsone 100 mg daily
  ± Pyrimethamine 50 mg weekly
• Pentamidine 300 mg (parenteral)
• Clindamycin + primaquine
• Clindamycin + Caspofungin
• Atovaquone 750 mg twice daily (oral)

Question 12

Adjunctive Corticosteroids

Answer 12

Indication
* Severe PJP
* ICU-level hypoxia

ATS-recommended regimen (21 days)
* Prednisone 40 mg BD days 1–5
* 40 mg daily days 6–11
* 20 mg daily days 12–21